Temozolomide: therapeutic limitations in the treatment of adult high-grade gliomas

Abstract

Temozolomide-based chemotherapy represents an incremental improvement in the treatment of patients with high-grade gliomas. Notwithstanding a survival benefit in a subset of patients with high-grade gliomas, temozolomide (TMZ; Temodar^®, Schering-Plough Pharmaceuticals, NJ, USA) is the primarily palliative treatment for the vast majority of patients. Indeed, for patients with newly diagnosed glioblastoma, the median increase in survival for treatment with TMZ and radiotherapy is only 2.5 months compared with radiotherapy alone. Additionally, recent studies suggest that 60–75% of patients with glioblastoma derive no benefit from treatment with TMZ. For the treatment of recurrent anaplastic gliomas, more than 50% of patients fail TMZ treatment with cancer progression at 6 months, demonstrating that TMZ is only a modestly effective chemotherapy. In addition, 15–20% of patients treated with TMZ develop clinically significant toxicity, which can leave further treatment unsafe. Despite the availability of TMZ, there is still a substantial need for a chemotherapeutic agent that is more effective and safe. In fact, there still remains a significant unmet need for more effective treatments of high-grade gliomas (improved palliation or cure), whether that treatment be by surgery, radiotherapy, chemotherapy or any yet to be developed type of treatment, such as ‘targeted therapies’.

Keywords::

• alkylator-based therapy for gliomas
• high-grade gliomas
• temozolomide chemotherapy
• temozolomide-based chemotherapy

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.